Uninflated Cuff Research Articles

Is Cardiac Remote Ischemic Preconditioning (RIPC) More Beneficial in Patients with Diabetes to Reduce Cardiac Troponin I After Elective Percutaneous Coronary Intervention (PCI)?

Background: Intervention of choice for reperfusion is percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), but it may have side effects; one of which is myocardial injury. Cardiac remote ischemic preconditioning (RIPC) can potentially reduce these adverse effects, especially in patients with cardiovascular risk factors. Methods: This study received ethics approval on November 29, 2017 (ethics code: HUMS.REC.1396.93; IRCT code: IRCT20180306038978N1). It was performed on 240 patients (120 cases in the RIPC group and 120 cases in the control group). The patients undergoing PCI were randomly assigned to the RIPC group (blood pressure cuff was inflated up to 200 mmHg for 30 minutes on the non-dominant arm, and then deflated for 5 minutes (reperfusion); it was repeated 2 more times (3 times in general) or the control group (an uninflated cuff around the non-dominant arm). Cardiac troponin I (cTnI) was compared between the healthy controls and diabetic patients before and after PCI. Results: No significant difference was observed with regard to positive cTnI (P = 0.136). Positive cTnI was insignificantly higher in the control group compared to the intervention group. However, the frequency of positive cTnI was significantly lower in diabetic patients in the RIPC group compared to the controls (P < 0.001). Conclusions: This study demonstrated that RIPC is beneficial in diabetic patients and reduces the release of cTnI after elective PCI in these patients.

The Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial.

Remote ischemic preconditioning (RIPC) protects other organs from subsequent lethal ischemic injury, but uncertainty remains. We investigated if RIPC could prevent acute kidney injury (AKI) in patients undergoing coronary artery bypass graft (CABG) surgery. This parallel-group, double-blind, randomized, controlled trial was done on adults undergoing elective or urgent on-pump CABG surgery from 2013 to 2017 in Shiraz, Iran. Patients were allocated to RIPC or control groups through permuted blocking. The patients in the RIPC group received three cycles of 5 min ischemia and 5 min reperfusion in the upper arm after induction of anesthesia. We placed an uninflated cuff on the arm for 30 min in the control group. The study primary endpoint was an incidence of AKI. Secondary endpoints included short-term clinical outcomes. We compared categorical and continuous variables using Pearson χ2 and unpaired t tests, respectively. P<0.05 was considered significant. of the 180 patients randomized to RIPC (n=90) and control (n=90) groups, 87 patients in the RIPC and 90 patients in the control group were included in the analysis. There was no significant difference in the incidence of AKI between the groups (38 patients [43.7%] in the RIPC group and 41 patients [45.6%] in the control group; relative risk, 0.96; 95% confidence interval, 0.69 to 1.33; P=0.80). No significant differences were seen regarding secondary endpoints such as postoperative liver function, atrial fibrillation, and inpatient mortality. RIPC did not reduce the incidence of AKI, neither did it improve short-term clinical outcomes in patients undergoing on-pump CABG surgery. Trial Registration Number: IRCT2017110537254N1.

Effects of remote ischemic preconditioning on contrast induced nephropathy after percutaneous coronary intervention in patients with acute coronary syndrome.

Objective:The aim of this study was to explore the clinical effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).Patients and Methods:The study was a single-center, prospective, randomized, controlled study. A total of 161 patients with ACS and the rate of estimate glomerular filtration (eGFR) 15 to 70 mL/min/1.73 m2 undergoing PCI were randomly assigned to RIPC group (induced by 4 times of 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion at 1 hour before PCI therapy) or control group (an uninflated cuff around the arm). Successful completion of the PCI eventually included 107 cases of patients, including 50 cases in the RIPC group and 57 cases in the control group. The level of serum creatinine (Scr), CystatinC (CysC), blood neutrophil gelatinase-associated lipocalin (NGAL), eGFR were measured in all patients at 6 am before the day of PCI, and 4-hour NGAL, 24-hour CysC, 72-hour Scr, and eGFR after PCI in the 2 groups. The incidence of major adverse events in the kidney (including the incidence of CIN, the need for dialysis, or renal replacement therapy after using contrast agent) and the composite endpoint of cardiovascular events were recorded at 6 months after PCI.Results:There were no statistically significant differences in baseline indicators between the 2 groups. Scr, CysC, and blood NGAL levels and the incidence of CIN in patients with RIPC group were significantly lower than those form the control group after PCI (P < .05), but there were no significant differences between the average value of eGFR and occurrence of Major cardiovascular events in the postoperative 6 months (P > .05).Conclusions:RIPC can reduce PCI-related CIN and protect renal function in patients with ACS. The benefits of these patients by RIPC may be related to the reduction of the NGAL and CysC.

Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction.

This study aimed to determine whether remote ischemic conditioning (RIC) initiated prior to primary percutaneous coronary intervention (PPCI) could reduce myocardial infarct (MI) size in patients presenting with ST-segment elevation myocardial infarction. RIC, using transient limb ischemia and reperfusion, can protect the heart against acute ischemia-reperfusion injury. Whether RIC can reduce MI size, assessed by cardiac magnetic resonance (CMR), is unknown. We randomly assigned 197 ST-segment elevation myocardial infarction patients with TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 to receive RIC (four 5-min cycles of upper arm cuff inflation/deflation) or control (uninflated cuff placed on upper arm for 40 min) protocols prior to PPCI. The primary study endpoint was MI size, measured by CMR in 83 subjects on days 3 to 6 after admission. RIC reduced MI size by 27%, when compared with the MI size of control subjects (18.0 ± 10% [n = 40] vs. 24.5 ± 12.0% [n = 43]; p = 0.009). At 24 h, high-sensitivity troponin T was lower with RIC (2,296 ± 263 ng/l [n = 89] vs. 2,736 ± 325 ng/l [n = 84]; p = 0.037). RIC also reduced the extent of myocardial edema measured by T2-mapping CMR (28.5 ± 9.0% vs. 35.1 ± 10.0%; p = 0.003) and lowered mean T2 values (68.7 ± 5.8 ms vs. 73.1 ± 6.1 ms; p = 0.001), precluding the use of CMR edema imaging to correctly estimate the area at risk. Using CMR-independent coronary angiography jeopardy scores to estimate the area at risk, RIC, when compared with the control protocol, was found to significantly improve the myocardial salvage index (0.42 ± 0.29 vs. 0.28 ± 0.29; p = 0.03). This randomized study demonstrated that in ST-segment elevation myocardial infarction patients treated by PPCI, RIC, initiated prior to PPCI, reduced MI size, increased myocardial salvage, and reduced myocardial edema.

Late remote ischemic preconditioning provides benefit to patients undergoing elective percutaneous coronary intervention.

To assess whether late remote ischemic preconditioning (L-RIPC) is effective in myocardial protection in patients with ischemic heart disease undergoing elective percutaneous coronary intervention (PCI). L-RIPC is exerted by newly synthesized cardioprotective proteins. The cardioprotective effects of L-RIPC are more durable. 200 consecutive patients undergoing elective PCI were randomized to receive L-RIPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion) or control (an uninflated cuff around the arm) at 18 h before PCI. Creatine phosphokinase (CK), its cardiac isoenzyme (CK-MB), troponin I (TNI), and high-sensitivity C-reactive protein (hs-CRP) levels were measured at 24 h after PCI. Adverse events' rates at 6 months were assessed. Compared with the control group, patients in L-RIPC group were observed with significantly lower incidences in Chest pain score >1 and ECG ST deviation >1 mm (P < 0.05). The median TNI, CK, and CK-MB concentrations at 24 h were lower in the L-RIPC group (0.009 vs. 0.036 ng/mL, 123 vs. 186 IU/L, 15 vs. 27 IU/L; P < 0.05). There was no statistical difference in hs-CRP between two groups. At 6 months, the adverse events' rate was lower in the L-RIPC group (P = 0.036). L-RIPC is effective in myocardial protection in patients undergoing elective PCI and reduces adverse events' rate at 6 months.

CMR detects a reduction in infarct size and myocardial edema when primary PCI is augmented by Remote Ischemic Conditioning. A randomized trial

Background CMR is the imaging modality of choice to quantify myocardial injury in studies of cardioprotection. Remote ischemic conditioning (RIC), using transient limb ischemia and reperfusion, is a novel therapeutic intervention, which can protect the heart against acute ischemiareperfusion injury (IRI). Whether RIC can reduce myocardial infarct (MI) size, and improve myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI), is unknown, and was investigated in this randomized control clinical trial using CMR. Methods 323 consecutive patients with suspected STEMI were screened and randomized to receive either RIC (four-5 minute cycles of upper-arm cuff inflation/deflation) or control (un-inflated cuff) prior to PPCI. 197 met study inclusion criteria of confirmed STEMI with TIMI 0 flow. The primary study endpoint was MI size, measured by late gadolinium enhancement (LGE) on day 3-6. Myocardial edema was quantified for the first time in a clinical trial by T2 mapping, the extent of edema representing the area-at-risk (AAR). T2 values were assessed in remote myocardium and the area-at-risk, providing an additional surrogate marker for the amount of edema present. The Otsu thresholding technique was pre-validated as the most reproducible technique for quantification of both

Remote ischemic preconditioning is feasible in ad hoc percutaneous coronary interventions

Purpose: Percutaneous coronary intervention (PCI)-induced troponin cTnI release is associated with a worst prognosis. Recently, 3 cycles of 5-minute ischemia followed by 5-minute reperfusion of the upper extremities were shown to reduce troponin release in elective PCI. However, this ischemic preconditioning (IPC) protocol requires 30 minutes and is of limited use in the context of ad hoc PCI. Since experimental evidence suggests that IPC is a graded than an all-or-nothing phenomenon, and even a short, single IPC cycle may have protective effects in the myocardium, we hypothesized that patients undergoing ad hoc PCI would have reduced peri-procedural troponin release if subjected to a single, remote IPC cycle, between diagnostic catheterization and coronary intervention. Methods: Subjects were randomized to receive remote IPC (induced by one single 5-minute inflation of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 1 minute of reperfusion) or control (an uninflated cuff around the arm) in the catheter laboratory. The primary outcome was the difference between post-procedural cTnI (at 24 hours after PCI) and pre-procedural cTnI. Results: Ninety-three patients were included in the study (46 control group, 47 remote IPC group). Peri-procedural troponin release was significantly higher in the control group compared to the remote IPC group (0.49±0.42 vs. 0.10±0.19, p<0.001). No significant difference in ECG ST-segment deviation or ischemic discomfort was observed. Conclusion: One cycle of remote IPC attenuates procedure-related cTnI release, thus IPC may be feasible without introducing any delays in the catheter laboratory.

124 MULTI-LIMB REMOTE ISCHAEMIC PRECONDITIONING REDUCES MYOCARDIAL INJURY IN DIABETIC PATIENTS UNDERGOING CORONARY ARTERY BYPASS SURGERY

<h3>Background</h3> Diabetic patients undergoing coronary artery bypass surgery (CABG) are at higher risk of peri-operative myocardial injury (PMI) with subsequent worse short and long-term clinical outcomes. Remote ischaemic preconditioning (RIPC), in which the application of one or more brief cycles of non-lethal ischaemia and reperfusion to an organ or tissue protects the heart against a lethal episode of acute ischaemia-reperfusion injury, has emerged as a non-invasive, low-cost therapeutic intervention for protecting the heart in patients undergoing CABG surgery. However, both experimental and clinical studies have demonstrated that the diabetic heart presents an increased resistance to the protective effects of RIPC. Whether by increasing the preconditioning stimulus we can protect diabetic patients undergoing CABG surgery is unknown. <h3>Methods and results</h3> 87 consecutive diabetic patients undergoing elective CABG surgery were recruited into two substudies. In the first substudy (N=53), patients were randomised to receive either standard RIPC protocol (3–5 min cycles of upper arm cuff inflation to 200 mm Hg with intervening 5 min deflation, N=26) or control (uninflated cuff placed on the upper arm for 30 min, N=27) following anaesthesia induction. In the second substudy (N=34), patients were randomised to receive either an enhanced RIPC stimulus (2–5 min cycles of simultaneous upper arm and thigh cuff inflation to 200 mm Hg with intervening 5 min deflation, N=17) or control (uninflated cuffs placed on the upper arm and thigh for 20 min, N=17). PMI was calculated as area-under-the-curve (AUC) of troponin-T (TnT), measured pre-operatively and 6, 12, 24, 48, 72 h post-surgery. In the first substudy with standard preconditioning protocol, there was no difference in the 72 h TnT AUC between control and RIPC (AUC was respectively 22.17 µg/l and 22.22 µg/l, p=0.98). However, in the second substudy and with the application of the enhanced preconditioning stimulus, we observed a significant reduction in the 72 h TnT AUC in the RIPC group compared to control (31.73 µg/l vs 19.63 µg/l respectively, p=0.022). <h3>Conclusions</h3> An enhanced preconditioning stimulus by multi-limb RIPC reduces PMI in diabetic patients undergoing CABG surgery. Larger multicentre studies are being conducted to confirm these studies.

Remote Ischemic Postconditioning: Does It Protect against Ischemic Damage in Percutaneous Coronary Revascularization? Justification and Design of a Randomized Placebo-Controlled Clinical Trial

Objective: Myocardial damage that is associated with percutaneous coronary intervention (PCI) partially affects the results of the procedure, and is related to medium-term cardiovascular death. Remote postischemic conditioning might reduce the myocardial lesions that are associated with PCI, but perhaps less so in diabetics. The aim of this study was to evaluate the protective effect of remote postischemic conditioning in patients undergoing elective PCI for stable angina or non-ST elevation acute coronary syndrome with troponin <1 ng/ml at the time of randomization. Methods: This randomized single-blinded single-center clinical trial involved 320 patients undergoing elective PCI who were randomized to either receive three 5-min cycles of ischemia by inflation of a cuff on the non-dominant arm to 200 mm Hg (remote postischemic conditioning) or to placebo (uninflated cuff). The primary outcome variable was the maximum increase in troponin in the first 24 h. The secondary outcome variable was readmission due to heart failure or cardiovascular mortality after 1 year of follow-up. In addition, a diabetic population was studied. Conclusions: This clinical trial evaluated the possible reduction in intervention-related myocardial damage that was attributable to remote postischemic conditioning.

Effect of Remote Ischemic Preconditioning on Acute Kidney Injury in Nondiabetic Patients Undergoing Coronary Artery Bypass Graft Surgery: A Secondary Analysis of 2 Small Randomized Trials

BackgroundNovel treatment strategies are required to reduce the development of acute kidney injury (AKI) in patients undergoing cardiac surgery. In this respect, remote ischemic preconditioning (RIPC), a phenomenon in which transient nonlethal ischemia applied to an organ or tissue protects another organ or tissue from subsequent lethal ischemic injury, is a potential renoprotective strategy.Study DesignSecondary analysis of 2 randomized trials.Setting & Participants78 consenting selected nondiabetic patients in a university teaching hospital undergoing elective coronary artery bypass graft (CABG) surgery recruited to 2 previously reported randomized studies.InterventionRIPC consisted of three 5-minute cycles of right forearm ischemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 minutes of reperfusion, during which time the cuff was deflated. The control consisted of placing an uninflated cuff on the arm for 30 minutes.OutcomesAKI measured using Acute Kidney Injury Network (AKIN) criteria, duration of hospital stay, in-hospital and 30-day mortality.ResultsNumbers of participants with AKI stages 1, 2, and 3 were 1 (3%), 3 (8%), and 0 in the intervention group compared with 10 (25%), 0, and 0 in the control group, respectively (P = 0.005). The decrease in AKI was independent of the effect of concomitant aortic valve replacement and cross-clamp times, which were distributed unevenly between the 2 groups.LimitationsRetrospective analysis of data. More patients in the RIPC group underwent concomitant aortic valve replacement with CABG; although we have corrected statistically for this imbalance, it remains an important confounding variable.ConclusionsRIPC induced using transient forearm ischemia decreased the incidence of AKI in nondiabetic patients undergoing elective CABG surgery in this retrospective analysis. A large prospective clinical trial is required to study this effect and clinical outcomes in patients undergoing cardiac surgery.

Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study

Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.

Intracerebroventricular micro-injections of non-steroidal anti-inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail

Prostaglandins are mediators of reperfusion hyperalgesia; their site of action may be in the periphery, in the central nervous system, or both. We have investigated whether prostaglandins play a role in the central nervous system during reperfusion hyperalgesia, by intracerebroventricular (i.c.v.) micro-injection of non-steroidal anti-inflammatory drugs (NSAID), to inhibit local prostanoid synthesis. We induced tail ischaemia in conscious rats by applying an inflatable cuff at the base of the tail. The cuff was released at the first signs of co-ordinated escape behaviour. Responses to a noxious thermal stimulus were assessed, by measuring tail flick latency following immersion of the tail in water at 49°C, prior to and immediately after release of the tourniquet. Tail flick latency decreased significantly following ischaemia, that is there was post-ischaemic reperfusion hyperalgesia. Intracerebroventricular micro-injection of NSAID prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia or on the tail flick latency after application of a sham tourniquet (uninflated cuff). However all the drugs abolished the hyperalgesia evident during reperfusion. Doses required to abolish hyperalgesia were 0.001 mg/kg indomethacin, 0.08 mg/kg dipyrone, 0.09 mg/kg ibuprofen, 0.2 mg/kg diclofenac sodium and 0.2 mg/kg paracetamol. These doses are 2–3 orders of magnitude less than those necessary to abolish reperfusion hyperalgesia when the same drugs are administered systemically. Our results indicate that the development of reperfusion hyperalgesia of the rat's tail depends on the synthesis of prostanoids within the central nervous system.

Role of the wrist cuff in forearm plethysmography

1. To determine whether a wrist cuff is necessary to measure the forearm blood flow correctly, we studied the effects of wrist cuff inflation to supra-venous and supra-systolic pressure values over a large range of forearm blood flow values: in the basal state, during post-occlusive hyperaemia of the hand, and during heating of the hand with warm air. Eleven healthy men participated, and the study was carried out at two different ambient temperatures of 20 and 25 degrees C. 2. In the basal state, the measured forearm blood flow was lowest with the wrist cuff at supra-systolic pressure. With the wrist cuff at supra-venous pressure the forearm blood flow was also lower than with an uninflated cuff, but only significantly so when the basal forearm blood flow was higher (at a room temperature of 25 degrees C). 3. During post-occlusive hyperaemia, inflating the wrist cuff to supra-systolic pressure produced the lowest forearm blood flow value at both room temperatures. In addition, with the wrist cuff at supra-venous pressure, forearm blood flow values were lower than with the uninflated cuff, but the supra-venous cuff pressure was clearly less efficient in excluding the hand blood flow than the supra-systolic cuff pressure. 4. During heating of the hand, both supra-systolic and supra-venous cuff pressures were effective in excluding the hand blood flow at both room temperatures. The forearm blood flow measured with the wrist cuff at supra-systolic pressure was lower than that measured with the wrist cuff at supra-venous pressure, but the difference was only significant at a room temperature of 20 degrees C. 5. In conclusion, we have demonstrated that a wrist cuff at supra-systolic pressure is most appropriate for the exclusion of the hand circulation in order to measure the forearm blood flow correctly.